应用化学2018，Vol.35Issue(4)：410-419,10.DOI:10.11944/j.issn.1000-0518.2018.04.170098
1,3-取代吲唑类低氧诱导因子l抑制剂的设计合成及其抗肝癌活性
Synthesis and Anti-Hepatoma Activities of 1,3-Substituted Indazole Derivatives as Hypoxia Induced Factor Inhibitors
摘要
Abstract
Hypoxia-inducible factor 1(HIF-1)is closely related to the growth,invasion and drug resistance of tumor cells and is highly expressed in tumor cells,so new HIF-1 inhibitors can be used as potential antitumor drugs.Nine 1,3-substituted indazole derivatives were synthesized.The expression of HIF-1 and its target gene vascular endothelial growth factor(VEGF)were detected by Western Blot and Real time-PCR(polymerase chain reaction),and the anti-tumor activities of all the newly synthesized compounds were evaluated on the in vitro growth of HepG2 cell line taking 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole(YC-1)(compound 7d)as positive control.We found that compound 7b significantly inhibited the expression of HIF-1 and its downstream target gene VEGF, and the anti-hepatoma biological activity in vitro of compound 7b was better than that of YC-1 with half maximal inhibitory concentration(IC50)values of 10.37 μmol/L.The results show that 3-(5'-hydroxy methyl-2'-furan)-1-(1'-p-tolylsulfonyl)indazole targets the inhibition of HIF activity,but also has a good anti-hepatoma activity.关键词
吲唑/HepG2细胞/低氧诱导因子l/抗肝癌活性Key words
indazole/hepG2 cells/hypoxia-inducible factor 1/anti-hepatoma activity分类
化学化工引用本文复制引用
李善花,李福男,黄志宁,苗方笑,郑满意,梁涵,王宝睿,曲宁,乔红,王海莉..1,3-取代吲唑类低氧诱导因子l抑制剂的设计合成及其抗肝癌活性[J].应用化学,2018,35(4):410-419,10.基金项目
福建省科技厅项目(2015Y0081,2015J01350) （2015Y0081,2015J01350）
厦门大学大学生创新创业训练计划项目(2016X0644,20720152005) Supported by the Natural Science Foundation of Fujian Province of China(No.2015Y0081,No.2015J01350),XMU Training Program of Innovation and Enterpreneurship for Undergraduates(No.2016X0644,No.20720152005) （2016X0644,20720152005）
